[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-355139-105":59,"doc-detail-355139-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-path-forward-for-t-cell-engagers-in-patients-with-prostate-cancer","The path forward for T cell engagers in patients with prostate cancer","","T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to drive antitumor immune responses. TCEs have shown promising clinical effects in metastatic castration-resistant prostate cancer and progressed into phase 3 trials. This review summarizes mechanisms for CD3- and CD28-targeted agents and reviews prostate cancer clinical development. A forward path is proposed to guide biomarker-driven patient selection, rational combinations, and toxicity-targeted treatments, enabling broader benefit for lethal prostate cancer.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-path-forward-for-t-cell-engagers-in-patients-with-prostate-cancer/355139/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-path-forward-for-t-cell-engagers-in-patients-with-prostate-cancer/355139.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of T cell engagers (TCEs) in prostate cancer?","Question",{"text":112,"@type":113},"TCEs aim to overcome immunosuppressive barriers by bringing T cells into the tumor microenvironment and facilitating T cell activation to promote antitumor responses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the prostate tumor microenvironment influence response to immunotherapy?",{"text":117,"@type":113},"Prostate cancer is described as an “immune desert,” with few intratumor effector T cells, low TMB and neoantigen formation, immunosuppressive myeloid cells, TGF-β signaling, and metabolic immunosuppression, leading to lower response rates to immune checkpoint therapies.",{"name":119,"@type":110,"acceptedAnswer":120},"Which two signals are required for classical T cell activation described in the review?",{"text":121,"@type":113},"Signal 1 is delivered when the TCR/CD3 complex recognizes antigen on MHC, and Signal 2 is a costimulatory signal delivered by receptors such as CD28 binding to B7 ligands (CD80/CD86); together they enable optimal activation and survival.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},355139,1790930171,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Open access Review  \n The path forward for T cell engagers inpatients with prostate cancer  \nSumit K Subudhi,1 Bilal A Siddiqui  ,1 Kevin K Zarrabi,2 William K Kelly,2 Charles G Drake3  \nTo cite: Subudhi SK, Siddiqui BA, Zarrabi KK, et al. The path forward for T cell engagers in patients with prostate cancer. Journal for ImmunoTherapy of Cancer 2026;14:e013905 . doi:10 . 1136/ jitc-2025-013905  \nSKS and BAS contributed equally.  \nAccepted 09 February 2026  \n© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \n1The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2Thomas Jefferson University, Philadelphia, Pennsylvania, USA 3Johnson & Johnson Innovative Medicine, Raritan, New Jersey, USA  \nCorrespondence to  \nDr Sumit K Subudhi;  \n[SKSubudhi@mdanderson.org](SKSubudhi@mdanderson.org)  \nAbstract T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to induce antitumor immune responses. TCEs have demonstrated promising clinical responses in patients with metastatic castrationresistant prostate cancer and have advanced into phase 3 clinical trials. Here we provide an overview of the mechanisms of action of TCEs, including both CD3-targeted and CD28-targeted agents, and review the clinical development of these agents for prostate cancer. We propose a path forward for TCEs in prostate cancer, in which innovative clinical trials will facilitate a biological understanding of mechanisms of efficacy and toxicity to inform: (1) development of predictive biomarkers for patient selection; (2) rational combination strategies; and (3) targeted treatments for toxicity management, ultimately delivering broad clinical benefit for patients with lethal prostate cancer.  \nTHE IMMUNOSUPPRESSIVE PROSTATE TUMOR MICROENVIRONMENT  \nIntratumoral effector T cells are required to mount effective antitumor immune responses. Cancers are classified by the degree of intratumoral T cell infiltration within the tumor microenvironment (TME), described as a “tumor immunity continuum” into: (1) inflamed; (2) immune-excluded; and (3) immune-desert.1 “‘Inflamed” cancers, such as melanoma, are characterized by a high degree of effector T cell infiltration, intact antigen presentation, induction of interferon gamma signaling and programmed death-ligand 1 (PD-L1) expression, all leading to relatively high rates of response to immune checkpoint therapies (ICTs) .1 “Immune-excluded”tumors are those in which effector T cells have accumulated at the invasive margin of the tumor but are unable to migrate into the tumor center, in part due to reactive stroma and high transforming growth factor (TGF)-β signaling, leading to low rates of response to ICTs.1 Finally,“immune desert” tumors are characterized by few overall effector T cells in the tumor center or periphery, with minimal responses to ICTs.1  \nProstate cancer generally falls into the“immune desert” category, with few intratumor effector T cells, low tumor mutational  \nburden (TMB) and neoantigen formation, high density of immunosuppressive myeloid cells, suppressive cytokines such as TGF-β, and metabolic pathways such as adenosine signaling.2–4 Accordingly, response rates to ICTs with prostate cancer have been markedly lower than for those of inflamed tumor types, ranging from 3% to 5% with single-agent anti-programmed cell death protein-1 (PD-1) therapies to up to 25% with combination anticytotoxic T-lymphocyte associated protein 4 (CTLA-4) and anti-PD-(L)1 therapy.5–8  \nPRINCIPLES OF T CELL ENGAGERS  \nT cell engagers (TCEs) aim to overcome these immunosuppressive barriers by directly bringing T cells into the TME. TCEs are designed so that one domain binds to a protein expressed on T cells, whereas the other binds to a protein expressed on tumor cells. To induce an effective antitumor immune response, TCEs must not only induce proximity between T cells and tumor cells but must also ","cbCaisCQxmu9PMGm","https://ap.wps.com/l/cbCaisCQxmu9PMGm","pdf",948975,14,"English","# Abstract\n# The immunosuppressive prostate tumor microenvironment\n## Tumor immunity continuum: inflamed, immune-excluded, immune-desert\n## Immunosuppressive features and limited checkpoint responses\n# Principles of T cell engagers\n## Bispecific design and requirements for activation\n## Classical T cell activation signals: Signal 1 and Signal 2\n## Current and emerging TCE targets (CD3, CD28, 4-1BB, γδ T cells)","[{\"question\":\"What is the main goal of T cell engagers (TCEs) in prostate cancer?\",\"answer\":\"TCEs aim to overcome immunosuppressive barriers by bringing T cells into the tumor microenvironment and facilitating T cell activation to promote antitumor responses.\"},{\"question\":\"How does the prostate tumor microenvironment influence response to immunotherapy?\",\"answer\":\"Prostate cancer is described as an “immune desert,” with few intratumor effector T cells, low TMB and neoantigen formation, immunosuppressive myeloid cells, TGF-β signaling, and metabolic immunosuppression, leading to lower response rates to immune checkpoint therapies.\"},{\"question\":\"Which two signals are required for classical T cell activation described in the review?\",\"answer\":\"Signal 1 is delivered when the TCR/CD3 complex recognizes antigen on MHC, and Signal 2 is a costimulatory signal delivered by receptors such as CD28 binding to B7 ligands (CD80/CD86); together they enable optimal activation and survival.\"}]","The path forward for T cell engagers in patients with prostate cancer | PDF",1790116291,35]